1. Field of the Invention
This invention relates to a novel process for the displacement of the acetoxy group of a 7-aminocephalosporanic acid and, more particularly, to a novel process of producing 7-amino-3-heterocyclic thiomethyl-.DELTA..sup.3 -cephem-4-carboxylic acids.
2. Description of the Prior Art
It is known to convert the acetoxymethyl group at the 3-position of a cephalosporanic acid to a heterocyclic thiomethyl group by reacting with a thiol as disclosed in U.S. Pat. No. 3,278,531. The inventors of the above-described patent report in other literature (J. D. Cooker, et al.; "Journal of Chemical Society"; 5015-5031(1965)) that the reaction is preferably performed, in general, in an aqueous medium under a neutral or basic condition at room temperature or a slightly lower temperature and when the reaction is performed under an acid condition, lactone is by-product and greatly reduces the yield for the desired product.
It is also known to perform the reaction of a 7-aminocephalosporanic acid having a free amino group at the 7-position and a thiol in the presence of boron trifluoride or the ether complex thereof to improve the yield (70-90%) as described in German Offenlegungsschrift No. 2,804,896 but this process encounters a difficulty in the point of using boron trifluoride which is a gaseous toxicant and the ether complex thereof shows strong inflammability.
It is further known that since a 7-aminocephalosporanic acid having a free amino group at the 7-position is insoluble in an organic solvent, the reaction of the aminocephalosporanic acid is preformed after improving the solubility thereof in an organic solvent by introducing thereto an acyl groups as disclosed in U.S. Pat. No. 4,144,391.
Under such a technical level, it has been desired for producing intermediates for obtaining useful cephalosporin derivatives to introduce a heterocyclic thiomethyl group to the 3-position of a 7-aminocephalosporanic acid having a free amino group at the 7-position thereof by a manner suitable for industrial practice.